Observational analysis shows decreased free-water in cholinergic nuclei in manifest and premanifest stages of Parkinson’s disease, suggesting early compensatory responses.
Motivation: Brain cholinergic function has not been investigated to date in LRRK2 mutation carriers with or without PD using free-water imaging. Goal(s): To investigate the effect of LRRK2 mutations on the cholinergic system in manifest and premanifest stages of PD using free-water imaging. Approach: We evaluated the effect of LRRK2 mutations on the cholinergic nuclei (i.e., Ch123, Ch4, and pedunculopontine nucleus) in manifest and premanifest stages of PD using free-water imaging. Results: LRRK2 mutation is associated with decreased free-water content in the Ch4 (also referred to as nucleus basalis of Meynert, nbM). Impact: This finding suggests early and sustained attempts to compensate for LRRK2-related dysfunction. Free-water imaging has the potential to be applied as a non-radiative imaging technique to identify asymptomatic LRRK2 mutation carriers.
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Wang et al. (2025) studied this question.
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